Project description:While dysbiosis and inflammation were previously implicated in cardiovascular diseases, the circuits of how microbiota drives distant perivascular innervation, neuroinflammation, and atherosclerosis remains unknown. Here, we report that IL-17RC signaling in the intestine protects from atherosclerosis controlling intestinal barrier and microbiota, and loss of IL-17RC in intestinal epithelial cells alters microbiota, enhances perivascular innervation and aortic inflammation, augmenting the disease. Neuronal outgrowth is functionally dependent on microbiota and is essential for neuroinflammation and augmentation of atherosclerosis as chemical denervation or chemogenetic inhibition reduces inflammation, macrophage activation and disease progression. Microbiota-dependent IL-17A producing gd T cells accumulate in the aorta to promote neuronal outgrowth and activation that can be reversed by gd T cell blockade. Perivascular neuron activation is further dependent on cell-autonomous IL-17 signaling as IL-17RC ablation in sympathetic neurons protected mice from microbiota-driven atherosclerosis. Together, our data illuminate how intestinal cytokine signaling distantly restrains neuroimmune interactions in aorta and uncovers a novel link between IL-17 signaling, microbiota, perivascular innervation and neuroimmune pro-inflammatory crosstalk instrumental for atherosclerosis progression.
Project description:This study is to compare the mRNA expression differences between atherosclerosis and non-atherosclerosis samples from female peripheral blood. The possible effects of races are also considered.
Project description:Genome-wide DNA methylation screening was performed using the Infinium HumanMethylation450 BeadChip in 34 samples of non-cancerous pancreatic tissue and 82 samples of cancerous tissue samples obtained from 82 patients with pancreatic ductal adenocarcinoma.
Project description:Eighteen samples were obtained from 9 patients who underwent delayed resection. The purpose of this study is to identify transcriptomic shifts in samples during therapy.
Project description:Atherosclerosis is fundamental in the development of cardiovascular disease. The unhealthy dietary habits, high fat and cholesterol intake could change the composition of gut microbes and metabolites which play a critical role in the development of atherosclerosis. To characterize the functionality of intestinal microbiome in the AS, we performed an analysis of microbiota proteins by a metaproteomics technique in 6 control samples and 6 feces samples. Using data dependent acquisition (DDA), a total of 8467 peptides with taxonomy annotation were identified and which were correspond to 3851 protein groups.